Review Article
Immune Checkpoint Inhibitors in Thoracic Malignancies: Review of the Existing Evidence by an IASLC Expert Panel and Recommendations

https://doi.org/10.1016/j.jtho.2020.03.006Get rights and content
Under an Elsevier user license
open archive

Abstract

In the past 10 years, a deeper understanding of the immune landscape of cancers, including immune evasion processes, has allowed the development of a new class of agents. The reactivation of host antitumor immune response offers the potential for long-term survival benefit in a portion of patients with thoracic malignancies.

The advent of programmed cell death protein 1/programmed death ligand-1 immune checkpoint inhibitors (ICIs), both as single agents and in combination with chemotherapy, and more recently, the combination of ICI, anti–programmed cell death protein 1, and anticytotoxic T-lymphocyte antigen 4 antibody, have led to breakthrough therapeutic advances for patients with advanced NSCLC, and to a lesser extent, patients with SCLC. Encouraging activity has recently emerged in pretreated patients with thymic carcinoma (TC). Conversely, in malignant pleural mesothelioma, pivotal positive signs of activity have not been fully confirmed in randomized trials. The additive effects of chemoradiation and immunotherapy suggested intriguing potential for therapeutic synergy with combination strategies. This has led to the introduction of ICI consolidation therapy in stage III NSCLC, creating a platform for future therapeutic developments in earlier-stage disease. Despite the definitive clinical benefit observed with ICI, primary and acquired resistance represent well-known biological phenomena, which may affect the therapeutic efficacy of these agents.

The development of innovative strategies to overcome ICI resistance, standardization of new patterns of ICI progression, identification of predictive biomarkers of response, optimal treatment duration, and characterization of ICI efficacy in special populations, represent crucial issues to be adequately addressed, with the aim of improving the therapeutic benefit of ICI in patients with thoracic malignancies.

In this article, an international panel of experts in the field of thoracic malignancies discussed these topics, evaluating currently available scientific evidence, with the final aim of providing clinical recommendations, which may guide oncologists in their current practice and elucidate future treatment strategies and research priorities.

Keywords

Non–small cell lung cancer
Small cell lung cancer
Consensus
Microbiome
Immune checkpoint inhibitors
Biomarkers

Cited by (0)

Drs. Remon and Passiglia contributed equally to this work.

Disclosure: Dr. Remon reports other support from MSD, Boehringer Ingelheim, Bristol-Myers Squibb, AstraZeneca, Roche Holdings, and Pfizer; and personal fees and nonfinancial support from OSE Immunotherapeutics, outside the submitted work. Dr. Barlesi reports personal fees from AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly Oncology, F. Hoffmann–La Roche Ltd., Novartis, Merck, MSD, Pierre Fabre, Pfizer, and Takeda; and grants from AbbVie, ACEA, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Eisai, Eli Lilly Oncology, F. Hoffmann-La Roche Ltd., Genentech, Ipsen, Ignyta, Innate Pharma, Loxo, Novartis, Medimmune, Merck, MSD, Pierre Fabre, Pfizer, Sanofi-Aventis, and Takeda, outside the submitted work. Dr. Forde reports grants and personal fees from AstraZeneca/Medimmune and Bristol-Myers Squibb; and grants from Kyowa Hakko Kirin, Novartis, and Corvus Pharmaceuticals, outside the submitted work. Dr. Garon reports personal fees from Dracen; grants and personal fees from EMD Serono and Novartis; and grants from BMS, Eli Lilly, Merck, AstraZeneca, Genentech, Mirati Iovance, Neon, and Dynavax, outside the submitted work. Dr. Gettinger reports other support from Bristol-Myers Squibb, Nektar, Genentech/Roche, Iovance Biotherapeutics, Takeda/ARIAD, and NextCure, outside the submitted work. Dr. Goldberg reports grants and personal fees from AstraZeneca; and personal fees from Eli Lilly, Bristol-Myers Squibb, Genentech, Amgen, Spectrum, and Boehringer Ingelheim, outside the submitted work. Dr. Herbst reports personal fees from AbbVie Pharmaceuticals and ARMO Biosciences; personal fees and other support from AstraZeneca, Merck and Company, Genentech/Roche, and Eli Lilly and Company; personal fees from Biodesix, Bolt Biotherapeutics, Bristol-Myers Squibb, EMD Serrano, Genmab, Halozyme, Heat Biologics, IMAB Biopharma, Immunocore, Infinity Pharmaceuticals; other support from Junshi Pharmaceuticals; and personal fees from Loxo Oncology, Midas Health Analytics, Mirati Therapeutics, Nektar, Neon Therapeutics, NextCure, Novartis, Pfizer, Sanofi, Seattle Genetics, Shire PLC, Spectrum Pharmaceuticals, Symphogen, Takeda, Tesaro, and Tocagen, outside the submitted work. Dr. Horn reports personal fees from AstraZeneca, Amgen, Genentech, Merck, Incyte, Pfizer, and Tessaro; grants and personal fees from Bristol-Myers Squibb; personal fees from EMD Serono; grants and personal fees from Xcovery; and grants from Boehringer Ingelheim, outside the submitted work. Dr. Kubota reports grants and personal fees from Ono and Boehringer Ingelheim; and personal fees from Chugai, MSD, AstraZeneca, Eli Lilly, Daiichi Sankyo, Bristol-Myers Squibb, Novartis, Kyowa Hakko Kirin, Eizai, and Taiho, outside the submitted work. Dr. Lu reports grants and personal fees from AstraZeneca, Roche, and Bristol-Myers Squibb, outside the submitted work. Dr. Mezquita reports personal fees from Roche Diagnostics; personal fees from Takeda; personal fees from Bristol-Myers Squibb; personal fees from Tecnofarma; other support from Bristol-Myers Squibb, Roche, and Chugai; and nonfinancial support from AstraZeneca, outside the submitted work. Dr. Paz-Ares reports other support from Genómica; personal fees from Eli Lilly; grants and personal fees from MSD, Bristol-Myers Squibb, and AstraZeneca; personal fees from Roche, Pharmamar, Merck, Novartis, Boehringer Ingelheim, Celgene, Servier, Sysmex Ipsen, Adacap, Sanofi, Bayer, and Blueprint; and other support from Altum Sequencing, outside the submitted work. Dr. Popat reports personal fees from Bristol-Myers Squibb, Roche, Takeda, AstraZeneca, Pfizer, MSD, EMD Serono, Guardant Health, AbbVie, Boehringer Ingelheim, OncLive, Medscape, and Incyte, outside the submitted work. Dr. Schalper reports personal fees from Clinica Alemana Santiago, Celgene, Moderna Therapeutics, Shattuck Labs, Pierre Fabre, AstraZeneca, Dyanamo Therapeutics, EMD Serono, Abbvie, Agenus, and Torque Therapeutics; and grants from Navigate Biopharma, Vasculox/Tioma, Tesaro, Onkaido Therapeutics, Takeda Pharmaceuticals, Surface Oncology, Pierre Fabre Research Institute, Merck, Bristol-Myers Squibb, AstraZeneca, and Eli Lilly, during the conduct of the study. In addition, Dr. Schalper has a patent (Prediction of Response to Immune-Modulatory Therapies) issued. Dr. Skoulidis reports nonfinancial support from Tango Therapeutics Inc., outside the submitted work. Dr. Reck reports personal fees from Abbvie, Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Merck, MSD, Novartis, Pfizer, and Roche, outside the submitted work. Dr. Scagliotti reports personal fees from AstraZeneca, Roche, and MSD during the conduct of the study; and personal fees from Eli Lilly, Takeda, and Pfizer, outside the submitted work. The remaining authors declare no conflict of interest.

© 2020 International Association for the Study of Lung Cancer. Published by Elsevier Inc.